Sensory reception in the end organs of taste involves a number of sequential steps. These steps include the initial transduction of ht chemical stimulus at the apical, chemosensitive tips of taste cells, the spread of receptor currents throughout the receptor cell, and finally, synaptic transmission from receptor cells to sensory afferent fibers. Recently, important additional steps in taste reception have come to be recognized. Namely, synaptic interactions are believed to occur within the peripheral sensory organ and neuromodulation of chemoreceptor responses is thought to take place. Such interactions may occur at synapses between taste bud cells, or at synapses from efferent sources onto taste cells. These synaptic interactions may help modify and shape the final signal output of the taste bud. There is compelling, but incomplete evidence for serotonin (5HT), acetylcholine (ACh), adenosine triphosphate (ATP), and adenosine (ADD) as transmitters or neuromodulators that modify signal processing in taste buds. There is also evidence that electrical synapses occur between taste bud cells and may modulate peripheral sensory processing. We propose to investigate chemical and electrical synaptic interactions in taste buds from rats and mudpuppies (Necturus maculosus), using intracellular and patch recording microelectrode techniques. We will test whether 5HT, ACh, ATP and ADD produce postsynaptic responses when they are focally applied to taste cells and if so, whether these junctions are affected by, and in turn, modify acid ("sour") stimulation. Additionally, we will investigate whether individual taste cells respond to a wide variety of taste stimuli or whether they are "turned" to discriminate a narrow spectrum of chemicals. Lastly, we propose to correlate structure with function by examining cells that have been characterized electrophysiologically and then viewing the same cells under the light and electron microscope. Our progress to date and our preliminary data convincingly show that all of the experiments proposed in this competitive renewal application are feasible. We have collected pilot data establishing that there may be significant synaptic interactions--both chemical (serotonergic and cholinergic) and electrical--within the end organs of taste. We have established that it is possible to correlate patch recordings with light and electron microscopy from the same cell to correlate structure with function. By the end of the proposed funding period, we hope to have a sound and detailed understanding of synaptic interactions at the cellular level, signal processing, and taste transduction in peripheral taste organs. The findings may allow researchers to devise peripheral-acting therapeutic agents that will modify taste reception, and perhaps even control food intake. These data may bear upon information processing in other end organs, not only for other chemoreceptors such as the carotid body, but also other sensory organs in hearing and vision.